PBA and other 4-chloro-2-fluoro-3-substituted-phenylboronic acids are useful intermediates in the preparation of 6-(poly-substituted aryl)-4-aminopicolinate compounds and 2-(poly-substituted aryl)-6-amino-4-pyrimidinecarboxylic acid compounds, which are useful as herbicides. The PBA or other 4-chloro-2-fluoro-3-substituted-phenylboronic acids may then be esterified using 1,3-propanediol to form (4-chloro-2-fluoro-3-substituted phenyl)-[1,3,2]-dioxaborinane (PBE).
PBA may be synthesized by reacting 2-chloro-6-fluoroanisole (2,6-CFA) with n-butyllithium (n-BuLi) and an electrophilic boronic acid derivative. Following subsequent reactions, the PBA is isolated as a solid. For example, the PBA can be extracted from an aqueous phase using ethyl acetate and concentrated to dryness. Alternatively, the solid PBA can be isolated by a crystallization process. The solid PBA can then be utilized as an intermediate in a subsequent reaction to form the 6-(4-chloro-2-fluoro-3 methoxyphenyl)-4-aminopicolinate compound or 2-(4-chloro-2-fluoro-3 methoxyphenyl)-6-amino-4-pyrimidinecarboxylic acid compound.
More specifically, PBA may be synthesized by reacting 2,6-CFA with n-BuLi and trimethyl borate B(OMe)3, adding an aqueous base to the reaction mixture, diluting the reaction mixture with acetonitrile (“MeCN”), and acidifying the reaction mixture with hydrochloric acid. The PBA can then be isolated by separating the MeCN and aqueous layers, providing an 80.3% yield of PBA.